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Objective: Mutations in Fused in Sarcoma (FUS or TLS) are the fourth most prevalent in Western European familial amyotrophic lateral sclerosis (ALS) populations and have been associated with causing both early and very late disease onset. FUS aggregation, DNA repair deficiency, and genomic instability are contributors to the pathophysiology of FUS‐ALS, but their clinical significance per se and their influence on the clinical variability have yet to be sufficiently investigated. The aim of this study was to analyze genotype–phenotype correlations and malignancy rates in a newly compiled FUS‐ALS cohort. Methods: We cross‐sectionally reviewed FUS‐ALS patient histories in a multicenter cohort with 36 novel cases and did a meta‐analysis of published FUS‐ALS cases reporting the largest genotype–phenotype correlation of FUS‐ALS. Results: The age of onset (median 39 years, range 11–80) was positively correlated with the disease duration. C‐terminal domain mutations were found in 90%. Among all, P525L and truncating/ frameshift mutations most frequently caused juvenile onset, rapid disease progression, and atypical ALS often associated with negative family history while the R521 mutation site was associated with late disease onset and pure spinal phenotype. Malignancies were found in one of 40 patients. Interpretation: We report the largest genotype–phenotype correlation of FUS‐ALS, which enables a careful prediction of the clinical course in newly diagnosed patients. In this cohort, FUS‐ALS patients did not have an increased risk for malignant diseases. [ABSTRACT FROM AUTHOR]

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The article presents a study aimed at identifying to which extent microstructural and effective disconnection of the corpus callosum (CC) are already present in patients with early relapsing-remitting multiple sclerosis (RRMS) prior to development of macroscopic CC lesion. Emphasis is placed on motor CC, a part that conveys interhemispheric motor information. It notes the application of a combined functional magnetic resonance imaging (fMRI)/diffusion tensor imaging (DTI) fiber-tracking procedure to determine the callosal motor fibers (CMFs).

H MRSI has evolved as an important tool to study the onset and progression of brain damage in multiple sclerosis. Abnormal increases in total creatine, total choline and myoinositol have been noted in multiple sclerosis. However, the pathobiochemical mechanisms related to these changes are still largely unclear. The combination of H MRSI and H-decoupled P MRSI can specify to what extent phosphorylated components of total creatine and total choline contribute to this increase. Combined H and P MRSI data were obtained at 3 T in 22 patients with multiple sclerosis and in 23 healthy controls, and aligned with structural MRI to allow for correction for partial volume effects caused by cerebrospinal fluid and lesion load. A significant increase in total creatine was found in multiple sclerosis, and this was attributed to equal changes in the phosphorylated and unphosphorylated components. The concentrations of the putative glial markers total creatine and myoinositol in lesion-free H MRSI voxels correlated with the global lesion load. We conclude that changes in total creatine are not related to altered energy metabolism, but rather indicate gliosis. Together with the increase in myoinositol, total creatine can be considered as a biomarker for disease severity. A significant total choline increase was mainly a result of choline components not visible by P MRS. The origin of this residual choline fraction remains to be investigated. Copyright © 2010 John Wiley & Sons, Ltd. H MR signal intensities of creatine, myoinositol and choline compounds are increased in brain tissue of patients with multiple sclerosis (MS). Although there is a concomitant increase in phosphorylated creatine, no corresponding changes are found for the sum of the phosphorylated choline compounds. We conclude that the pathological changes in total creatine in MS are not related to energy metabolism, but astrogliosis. The origin of this residual choline fraction {[total choline]-([phosphocholine]+[glycerophosphocholine])} remains to be investigated. [ABSTRACT FROM AUTHOR]

Electromyographic mirror activity (MA) refers to involuntary activation of the non-active limb during intended strictly unilateral movements of the other limb. MA occurs in the majority of healthy adults but little is known about its neurophysiological foundation. Here we examined in healthy adults the hypothesis that transcallosal interhemispheric inhibition (IHI) between the primary motor cortices determines the extent to which MA occurs. IHI was tested by an established paired transcranial magnetic stimulation protocol [A. Ferbert et al. (1992) J. Physiol. (Lond.), 453, 525–546]. In a first experiment we found that the magnitudes of IHI and MA were inversely correlated. In a second experiment we sought to establish a more causative relation by exploring the changes induced by low-frequency repetitive transcranial magnetic stimulation of primary motor cortex on IHI and MA. These changes were also significantly inversely correlated, i.e. a repetitive transcranial magnetic stimulation-induced increase in IHI was associated with a decrease in MA, and a decrease in IHI was associated with an increase in MA. These results provide strong and consistent evidence that transcallosal inhibitory interhemispheric interaction provides a significant route by which unwanted MA during intended unimanual motor tasks can be controlled. [ABSTRACT FROM AUTHOR]